Tumor gene therapy made easy: Allogeneic major histocompatibility complex in the C6 rat glioma model

The C6 glioma in the immune-competent rat is a frequently used model in bra in tumor gene therapy research. It displays the histologic hallmarks of the human glioblastoma and has been employed to demonstrate new mechanisms of anti-tumor immunity and therapeutic strategies. We noted that C6 tumors reg ressed spontaneously in three of five animals and that protective anti-tumo r immunity ensued without therapeutic intervention. A review of the literat ure revealed that different rat strains are used as "syngeneic" host for th e C6 cell glioma, namely, BDM, BDX, Sprague-Dawley, and Wistar, Allelotypin g of the RT1.A (rat MHC I homolog) by a serologic technique and of the RT1. B (rat MHC II homolog) by a newly developed molecular technique showed that C6 cells express the haplotype RT1(u) and are allogeneic in the preceding rat strains. Expression of the gene encoding the transactivator CIITA in C6 gliomas using an EBV-based transduction system led to induction of MHC I a nd II and thereby mimicked therapeutic responses that could not operate in syngeneic models. These data suggest that the C6 glioma model in the immune -competent rat should no longer be used to study gene therapy strategies, t hat the available data obtained in this model need to be critically reinter preted, and that findings obtained in the C6 glioma model may not be suffic ient to support a clinical trial in glioblastoma patients.